The objective of the Imaging Core is to provide individual projects with unique in vivo monitoring capability for sequential and real-time tracking of the transit and localization of genetically altered T- lymphocytes, bone marrow-derived progenitor cells, endothelial cells and tumor cells by noninvasive imaging. This will be accomplished by monitoring the expression of single and multi-modality reporter genes, using optical (bioluminescence and fluorescence), radionuclide (PET, SPECT and quantitative autoradiography), magnetic resonance (MRI and MRS) and CT imaging. These non-invasive imaging techniques are well established at Memorial Sloan Kettering Cancer Center (MSKCC) for both small-animal and patient imaging studies. We propose a two-step strategy: first, to establish and validate our imaging objectives in experimental animals, and second, to translate selected aspects of our imaging technology to patient studies within the context of the projects proposed in this application. We propose to develop and validated a number of hybrid reporter genes that allow for multi-modality in vivo imaging in small animals. Two fusion reporter genes, RFP-hRLuc and eGFP-FLuc, have been developed with the Retroviral Core and they are undergoing initial testing and validation;others are planned for development and assessment. The first clinical studies to image the trafficking of donor T lymphocytes that have been sensitized with autologous EBV transformed Blymphocyte cell line (EBV BLCL) and transduced with the NIT vector (that encodes a surface receptor (LNGFR) for selection and a reporter gene (HSV1 thymidine kinase, HSV1-tk) for noninvasive imaging is proposed for patients undergoing adoptive treatment EBV lymphomas. The administered donor T lymphocytes will be noninvasively monitored with [124I]-FIAU (a radiolabeled probe that is selectively phosphorylated by HSV1-TK and trapped in transduced cells) and PET imaging.